Immunolocalization of transitional cell carcinoma of the bladder with intravesically administered technetium-99m labelled HMFG1 monoclonal antibody

Abstract

The aim of this study was the immunolocalization of transitional cell carcinoma of the bladder with a radiolabelled murine tumour-associated monoclonal antibody and the measurement of the absolute uptake of the antibody by the tumour. Fourteen patients with transitional cell carcinoma of the bladder received 3-6 mCi (111-222 MBq) of technetium-99m labelled HMFG1 monoclonal antibody intravesically and one patient, 2 mCi (74 MBq) of iodine-131 labelled 11.4.1, which is a non-tumour-specific monoclonal antibody. Four of the 15 patients were evaluated with single-photon emission tomography (SPET) 1 1/2 to 2 h post administration. All patients underwent transurethral resection of the bladder tumour within 12-20 h following intravesical administration of the radiolabelled antibody. The radioactivity of biopsy specimens from normal urothelium and tumour areas were counted in a gamma counter. The mean uptake of the radiolabelled antibodies from normal and tumour sites was expressed as a percentage of the administered dose per kilogram of tissue. Conventional histology and immunohistochemistry using HMFG1 monoclonal antibody were performed on paraffin sections of the biopsy specimens. Although our results are preliminary, it can be concluded that: (a) bladder tumours are well imaged by SPET when using 99mTc-HMFG1; (b) intravesically administered radiolabelled antibody remains on the bladder tissue and does not escape into the systemic circulation; (c) the wide range of tumour uptake values (0%-9.3% administered dose/kg) observed probably can be attributed to heterogeneity of the antigenic expression of the tumour; (d) values of 99mTc-HMFG1 monoclonal antibody uptake by the tumour do not justify future attempts at radioimmunotherapy.

Labeling of anti‐elastin antibody with technetium‐99m

“…This fact is also observed in blood and urine. These results are in agreement with other authors [5,6,7] using different antibodies.…”

Review:Intracavitary Radioimmunotherapy to Treat Solid Tumors

“…101 In conclusion, intravesically administered RIS in bladder cancer may hold a promise for RIT, using anti-MUC1 antibodies, in early urothelial cell cancer owing to selective targeting and low systemic concentrations of the targeting agent.…”

Enhancing Therapeutic Efficacy and Safety of Immune Checkpoint Inhibition for Bladder Cancer: A Comparative Analysis of Injectable vs. Intravesical Administration

“…Not only is the Stokesian diffusion of macromolecules-BCG, pembrolizumab and EGF conjugated probe (Figure 1)-slower than that of smaller molecules like Mitomycin [molecular weight 334.3 Daltons, partition coefficient (log P)-0.4] [ [33][34][35] Gadobutrol [2,36] or fluorescein [37] but the extravasation of diffused macromolecules into capillaries and veins is slower than small molecules. As a result, fast venous clearance of Mitomycin [33,34], Gadobutrol [38] or Fluorescein [37] prevents their excessive buildup in the lesioned areas whereas slow lymphatic clearance of macromolecules [39] engenders a 2.4-1710-fold uptake of EGF conjugated probe relative to normal areas which reproduced the excessive buildup of labeled antibodies in transected lesions [32,40,41].…”

“…ICE-MRI may be also able to Therefore, the undetectable blood levels of pembrolizumab after intravesical administration [17] need to be reconciled with the quantification of 0.01% instilled dose of radioiodinated albumin in the plasma of BC patients [30]. Based on pharmacokinetics of similar sized macromolecules, we estimate that the absorbed dose fraction of intravesical pembrolizumab is likely to be larger than 0.01% owing to BCG-evoked inflammation accelerating the paracellular diffusion but slower lymphatic clearance extending the pharmacokinetic and pharmacodynamic effects of pembrolizumab after single dose [32,[39][40][41]47,51].…”